Reward motivation adaptation in people with negative schizotypal features: development of a novel behavioural paradigm and identifying its neural correlates using resting-state functional connectivity analysis.

Reward motivation in individuals with high levels of negative schizotypal traits (NS) has been found to be lower than that in their counterparts. But it is unclear that whether their reward motivation adaptively changes with external effort-reward ratio, and what resting-state functional connectivity (rsFC) is associated with this change. Thirty-five individuals with high levels of NS and 44 individuals with low levels of NS were recruited. A 3T resting-state functional brain scan and a novel reward motivation adaptation behavioural task were administrated in all participants. The behavioural task was manipulated with three conditions (effort > reward condition vs. effort < reward condition vs. effort = reward condition). Under each condition were rated 'wanting' and 'liking' for rewards. The seed-based voxel-wise rsFC analysis was conducted to explore the rsFCs associated with the 'wanting' and 'liking' ratings in individuals with high levels of NS. 'Wanting' and 'liking' ratings of individuals with high levels of NS significantly declined in the effort > reward condition but did not rebound as high as their counterparts in the effort < reward condition. The rsFCs in NS group associated with these ratings were altered. The altered rsFCs in NS group involved regions in the prefrontal lobe, dopaminergic brain regions (ventral tegmental area, substantia nigra), hippocampus, thalamus and cerebellum. Individuals with high levels of NS manifested their reward motivation adaptation impairment as a failure of adjustment adaptively during effort-reward imbalance condition and altered rsFCs in prefrontal, dopaminergic and other brain regions.

Urinary Concentrations of Organophosphate Flame-Retardant Metabolites in the US Population.

Importance: Organophosphate flame retardants (OPFRs) are an important group of pollutants associated with endocrine disorders, cancer, and nephrotoxicity. However, temporal trends in OPFR metabolite concentrations remain understudied. Objectives: To examine changes in urinary concentrations of OPFR metabolites among US children, youths, and adults from 2011 to 2020, and to evaluate whether sociodemographic factors were associated with variations in temporal trends. Design, Setting, and Participants: This population-based cross-sectional study used data from 4 US National Health and Nutrition Examination Survey (NHANES) cycles (2011-2012, 2013-2014, 2015-2016, and 2017-2020 [to March 2020 before the COVID-19 pandemic]). The study included children and youths (aged 6-19 years) and adults (aged ≥20 years) with valid urinary concentrations of the following OPFR metabolites: bis(2-chloroethyl) phosphate (BCEtP), bis(1-chloro-2-propyl) phosphate (BCPP), diphenyl phosphate (DPhP), and dibutyl phosphate (DBuP). Data analysis was performed between February and May 2024. Exposures: Calendar year and key sociodemographic subgroups (age, race and ethnicity, sex, educational attainment, and poverty-to-income ratio). Main Outcomes and Measures: The main outcome was urinary concentrations of OPFR metabolites among children, youths, and adults. Survey-weighted linear regression models were applied to estimate trends. Results: The study population of 10 549 NHANES participants included 3154 children and youths (mean [SE] age, 12.5 [0.1] years; 51.2% were male) and 7395 adults (mean [SE] age, 47.8 [0.4] years; 52.0% were women). Among children and youths, mean (95% CI) BCEtP concentrations decreased from 0.68 (0.60-0.77) µg/L in 2011-2012 to 0.41 (0.37-0.45) µg/L in 2017-2020 (P for trend < .001). Among adults, mean (95% CI) BCEtP concentrations decreased from 0.43 (0.37-0.50) µg/L in 2011-2012 to 0.29 (0.27-0.33) µg/L in 2017-2020 (P for trend < .001), and mean BCPP concentrations decreased from 0.15 (0.14-0.17) µg/L to 0.13 (0.12-0.14) µg/L (P for trend = .002). Parent level of educational attainment was associated with concentrations of BCPP and BCEtP among children and youths; however, no significant differences among adults were observed. Conclusions and Relevance: This study identified variations in temporal trends in urinary concentrations of OPFR metabolites among the US population from 2011 to 2020. In addition, substantial disparities in exposure levels persisted among children with different levels of parent educational attainment. These findings suggest that policy makers should consider socioeconomic factors to further reduce OPFR exposure and promote equity, ensuring a safe living environment for all individuals.

The prediction of effort-reward imbalance for reward motivation.

This sequential mediation analysis study examined how the baseline effort-reward imbalance (ERI) would predict reward motivation 1 year later in 435 college students. We found that negative/disorganized schizotypal traits and anticipatory pleasure experience together mediate the prediction of ERI for reward motivation.

Therapeutic Targets of Bufalin on Renal Carcinoma and Mechanisms: Experimental Validation of Network Pharmacology Analysis.

The possible targets underlying the activity of bufalin on renal cell carcinoma (RCC) were investigated using network pharmacology and experimental approaches. PharmMapper and other databases were explored for predicting the bufalin targets and RCC-related targets. Finally, the enriched pathways and the targets were analyzed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analyses. Furthermore, in vitro cell experiments were used to verify bufalin activation of AKT and MAPK signaling pathways in human mesangial cells. The therapeutic targets related to bufalin were identified via 35 intersecting targets. GO analysis identified 29 molecular functions, 16 cellular components, and 91 biological processes. KEGG pathway annotation identified 15 signal transduction pathways and 4 tumor-related pathways.

[Analysis of risk factors for selective devascularization in patients with portal hypertension].

OBJECTIVE: To investigate the risk factors for selective devascularization in patients with portal hypertension. METHODS: The clinical data of 160 patients with portal hypertension underwent selective devascularization were retrospectively analyzed. All the patients were divided into high-risk group and low-risk group according to the postoperative complications. Thirty-two clinical factors were analyzed using logistic regression. RESULTS: Single-factor analysis showed that history of jaundice, Child-Turcotte-Pugh classification, total bilirubin (before the operation), prolongation of prothrombin time, pre-operative free portal pressure, ascites, leukocyte count (1 week after the operation) and hemoglobin (1 week after the operation) were significantly different between the high-risk group and low-risk group (P < 0.05). Logistic regression analysis showed that decrease of free portal pressure, total bilirubin (before the operation), prolongation of prothrombin time, ascites, leukocyte count (1 week after the operation) and hemoglobin (1 week after the operation) were still significantly different between the two groups (chi2 = 53.337, P < 0.01). CONCLUSIONS: The risk factors of selective devascularization in patients with portal hypertension are decrease of free portal pressure, pre-operative total bilirubin, prolongation of prothrombin time, ascites, post-operative leukocyte count and hemoglobin.

Clinical factors that influence the outcome of selective devascularization in the treatment of portal hypertension.

There is a high incidence of death due to variceal hemorrhage in patients with portal hypertension. Factors to consider when choosing selective devascularization in the treatment of variceal hemorrhage remain a controversy. This study aims to generate the prevalent clinical risk factors that affect the outcomes of selective devascularization procedures. Elucidating these features may guide future treatment of esophageal varices in patients with portal hypertension. We retrospectively analyzed medical records of 455 patients who underwent selective devascularization procedures in our center. Patients were subject to splenectomy, selective devascularization with or without esophageal transection. The mode of surgery recurred in comparable rates in both the group with major complications postoperatively (high-risk group which consisted of 63 patients) or the group without major postoperative complications (low-risk group, 392). Risk factors that negatively influenced outcomes of surgery include severe symptoms (89% in high risk group and 71% in low risk group), large volume of blood loss in the hemorrhage before surgery (81% in high risk group and 16% in low risk group), sever liver cirrhosis (83% in high risk group and 67% in low risk group), previous endotherapy, prolonged prothrombin time, and poor liver function. Selective devascularization is a feasible option to treat variceal hemorrhage in patients with portal hypertension.

Caveolin-1 is important for nitric oxide-mediated angiogenesis in fibrin gels with human umbilical vein endothelial cells.

AIM: The role of caveolin-1 (Cav-1) in angiogenesis remains poorly understood. The endothelial nitric oxide (NO) synthase (eNOS), a caveolin-interacting protein, was demonstrated to play a predominant role in vascular endothelial growth factor (VEGF) -induced angiogenesis. The purpose of our study was to examine the role of Cav-1 and the eNOS complex in NO-mediated angiogenesis. METHODS: Human umbilical vein endothelial cells (HUVEC) were isolated and cultured in 3-D fibrin gels to form capillary-like tubules by VEGF stimulation. The expression of Cav-1 and eNOS was detected by semiquantitative RT-PCR. The HUVEC were treated with antisense oligonucleotides to downregulate Cav-1 expression. Both transduced and non-infected HUVEC were cultured in fibrin gels in the presence or absence of VEGF (20 ng/mL) and NG-nitro-L-arginine methyl ester (L-NAME; 5 mmol/L). NO was measured using a NO assay kit and capillary-like tubules were quantified by tubule formation index using the Image J program. RESULTS: RT-PCR analysis revealed that Cav-1 levels steadily increased in a time-dependent manner and reached their maximum after 5 d of incubation, but there were no obvious changes in eNOS mRNA expression in response to VEGF in the fibrin gel model. VEGF (20 ng/mL) can promote NO production and the formation of capillary-like tubules, and this promoting effect of VEGF was blocked by the addition of L-NAME (5 mmol/L). When transduced HUVEC with the antisense Cav-1 oligonucleotides were plated in the fibrin gels, the capillary-like tubules were significantly fewer than those of the non-infected cells. The capillary-like tubules formation and NO production of transduced HUVEC with the antisense Cav-1 oligonucleotides cultured in fibrin gels showed no responses to the addition of VEGF (20 ng/mL) and L-NAME (5.0 mmol/L). CONCLUSION: NO was a critical angiogenic mediator in this model. Cav-1 was essential for NO-mediated angiogenesis and may be an important target of anti-angiogenesis therapy.